When people describe a company’s product as “amazing,” allowing them to “take back control of their life” or say it is “giving our daughter her life back”; when they fly in from points around the country for treatment; and when health care practitioners in countries around the planet are on a waiting list to learn how to use it, the company is probably onto something.
This describes Retraining and Control Therapy, or ReACT, the reason for being of the University of Alabama at Birmingham’s latest startup, ReACT FND Health. The company’s chief scientific officer and founder is clinical psychologist Aaron Fobian, Ph.D., associate professor in the Department of Psychiatry and Behavioral Neurobiology. Fobian developed ReACT to help patients with functional neurological disorder, or FND, which affects an estimated 300,000 Americans. In 2018, Fobian helped to begin an interdisciplinary treatment program at UAB to treat patients with FND; in 2020, she published the positive results of a 29-participant trial of ReACT that was the first randomized controlled trial of any treatment for pediatric functional seizures.
Symptoms of functional neurological disorder include seizure-like episodes, movement problems, dizziness, cognitive function difficulties, speech difficulties and other neurological symptoms.
Over the past 12 months, UAB’s Interdisciplinary Functional Neurological Disorder Treatment Program has treated 210 patients. And while Fobian continues to study ReACT through major NIH grants and ongoing clinical trials, the demand from patients and practitioners to access the treatment has been overwhelming. Thus, Fobian and clinical psychologist Areti Vassilopoulos, Ph.D., ReACT FND Health’s chief operating officer, are working to address that need.
“Our overall mission for ReACT FND Health is to be able to expand research-supported FND treatment to every individual in the United States with FND,” Fobian said. “Research-informed FND treatment is very difficult to find anywhere, and the symptoms themselves are incredibly debilitating to patients and their families. The symptoms keep children from being able to attend school and do things with their friends and keep adults from being able to go to work. It has a significant psychosocial and financial impact.”
An FND diagnosis costs families $87,000 per year to manage and the health care system $1.2 billion every year, Fobian says. “About 70 percent of adults with FND have to quit work, and the majority of our pediatric patients are not in school,” she said. “Our goal is to provide patients with treatment, so they are able to get back to their daily lives.”
ReACT FND Health, which launched in July through UAB’s Harbert Institute for Innovation and Entrepreneurship, will soon make treatment available through telemedicine for patients outside Alabama. By early 2025, it will begin training and certifying providers, drawing from a waiting list that includes practitioners across the country, as well as in Canada, Mexico, Brazil, the United Kingdom, Iceland, Australia and New Zealand.
“FND is the second most common diagnosis in neurology clinics and is especially prevalent in teenage girls. Currently, there is no other proven therapy that effectively treats FND,” said Kathy Nugent, Ph.D., executive director of the Harbert Institute. “We’re extremely supportive of ReACT’s mission, and proud that Dr. Fobian’s research at UAB provided the basis for this startup.”
Most behavioral health therapies are “manualized,” with a strict flow that practitioners must follow, Fobian explains. But ReACT, like functional neurological disorder, adapts from patient to patient and even from session to session if patients develop new symptoms, she says. In training the UAB clinical psychology doctoral students who help her see patients in the FND Treatment Program, Fobian has built out a complex adaptive digital treatment manual, called the ReACT Precision Treatment Tool. She contracted with a local design firm to create the Precision Treatment Tool.
“In general, the health care system does a really poor job of disseminating evidence-based mental health treatments,” Fobian said. “As they are disseminated, the fidelity of the intervention being provided decreases. A lot of times, it gets to the point where the patient may not be getting the treatment as it was originally designed. Our goal with ReACT FND Health is to disseminate this treatment with fidelity, to help therapists make decisions for this complex condition in-session so they can tailor the intervention to the precise symptoms that the patient has been having.”
In fact, the digital manual for ReACT, called the Precision Treatment Tool, is the first therapist-centered digital platform that is standardized and tailored to each individual patient’s needs at each individual session, Fobian says.
Another goal for the company is to reduce the time between diagnosis and treatment for patients, Fobian added: “We just published research showing that it is, on average, six months between when symptoms begin to when they start treatment and nearly one year between symptom onset and treatment onset for our pediatric patients. This can be even longer in adults. Our goal is to reduce those time frames, so we can prevent the psychosocial outcomes of being out of school or work for that long.”
There is an open secret among tattoo artists, dermatologists and the small group of researchers studying the effects of tattoo ink: Red ink causes the most problems.
Problems include rashes — itchy, sometimes painful and occasionally disfiguring — and pseudolymphomas — benign swellings around lymph nodes that resemble cancers of the lymph system. Both rashes and pseudolymphomas are symptoms of an allergic reaction. While these problems are not unique to red ink, red is the most likely culprit. Now, one student from the University of Alabama at Birmingham is on a mission to understand why.
Doctors are more likely to see tattoo complications now than ever before. Thirty percent of Americans have at least one tattoo, up from 21 percent in 2012, according to a 2019 poll.
A separate study in 2017 estimated the range of post-tattoo complications at anywhere from 2 percent to 30 percent; in that paper’s review of patient cases in Finland, 75 percent of allergic reactions were against the red color.
Until the mid-20th century, the reason for red’s ravages was clear: Red tattoo inks often contained mercury. But as the adverse effects of mercury and other metals became widely known, tattoo artists avoided these inks and manufacturers turned to alternative formulas. Today, manufacturers have largely switched to inks colored by organic compounds instead of compounds including heavy metals, and recent studies have found low concentrations of mercury in commercial inks. But red ink is still the most likely color to cause skin problems.
“I just had to know why”
Tiffany Mayo, M.D., associate professor and director of the UAB Department of Dermatology’s Clinical Research unit, discussed this puzzle last year during a lecture to third-year students at the UAB Marnix E. Heersink School of Medicine. Her description and slides immediately caught the attention of Matthew Kiszla, an artist and son of an artist who had cheekily listed a book that he and his mother illustrated among the publications on his med school application.
“I am a very visual person,” Kiszla said, and even though he does not have any tattoos himself, “that attracts me to tattoos and also to dermatology, with its vivid, dramatic rashes.” Plus, Kiszla was an undergraduate chemistry major. The chemical mystery that Mayo described was irresistible, he said: “I just had to know why.”
Kiszla’s interest has become a passion to understand the effects of tattoo inks on human health and to advocate for increased attention to safety. This February, Kiszla, Mayo and another member of the Department of Dermatology, Professor Craig Elmets, M.D., synthesized results from nine recent studies of tattoo inks worldwide in a review article published in the journal Chemosphere. “Unsafe levels of restricted elements” — including chromium, cadmium, barium, arsenic and zinc — “continue to be detected across studies, warranting further investigation under a regulatory lens,” they wrote.
“Although the United States is the world’s foremost producer of tattoo inks, they are virtually unregulated at a national level,” Kiszla said. “Tattoo inks can be formulated with a wide range of pigments, preservatives, solvents and other contaminants, which have been associated with rashes that range from transient to disfiguring.”
And there may be other, hidden effects as well.
“The potential systemic implications are unknown,” Kiszla said. “While researchers have found that ink can travel from its site of injection via the lymphatic system and be collected into lymph nodes, they have yet to determine whether this concentration of toxins poses any increased risk.”
Coincidence or something more?
Kiszla says Europe, the world’s second-largest market for tattoo ink manufacturers, leads the way in terms of research and regulation.
A series of resolutions introduced in Europe starting in 2003 set maximum allowed concentrations for tattoo ink ingredients; in 2022, these guidelines became binding on all members of the European Union. Nearly all research on the chemical makeup of tattoo inks has been done at European universities, Kiszla notes. In their Chemosphere paper, Kiszla, Mayo and Elmets compared these new European regulations with the concentrations of metals found in tattoo inks as reported in published studies.
Now Kiszla has turned his attention to organic inks. He is currently writing a paper on azo dyes with Lauren Kole, M.D., an assistant professor in the UAB Department of Dermatology — who, like Kiszla, holds an undergraduate degree in chemistry. Organic azo dyes are the new standard for tattoo inks as the industry has shifted from metal-based inks.
“Warm tones — yellow, orange and red — have a high concentration of these azo structures,” Kiszla said.
Kiszla says the fact that red inks still cause the most adverse reactions, as they did in the days of mercury, could just be a coincidence but says there is not yet enough data to be sure.
Tattoo research needs collaborators
While the published studies that Kiszla, Mayo and Elmets evaluated did include some commercial tattoo inks, they were not comprehensive. With grant support from the University of Alabama’s College of Community Health Sciences, Kiszla aims to analyze more tattoo inks and hopes to work with tattoo artists in the community on the project.
“Ultimately, I want to support the development of safer tattoo inks,” Kiszla said. “My goal is not to impinge on artistic expression but to make body art as safe as possible and as well understood as possible.”
(Courtesy of UAB)
In the immediate aftermath of a snakebite, a natural question is “Will I die?”
The answer is, very likely, no, even if the snake is venomous. Only about five people die per year from snakebite in the United States. So, once the initial shock has passed, there is a better question to ask: “Will I be maimed for life?”
“So many people — in the Southeastern United States, especially — have persistent wounds, bad swelling and morbidity issues after snake envenomation, and there was no good place to send them for follow-up,” said Dr. William Rushton, associate professor in the University of Alabama at Birmingham Department of Emergency Medicine in the Marnix E. Heersink School of Medicine.
Rushton is a medical toxicologist and the medical director of the Alabama Poison Information Center, the state’s poison control center, based at Children’s of Alabama. Nearly all snakebites in Alabama trigger a call to APIC. In the heart of snakebite season, Rushton and fellow medical toxicologist Dr. Sukhshant Atti average one or two snakebite consults every day with providers throughout the state.
Nothing like it elsewhere
Last year, Rushton and wound-care expert Dr. Dag Shapshak, associate professor in the Department of Emergency Medicine, launched the first-of-its-kind UAB Comprehensive Snakebite Program, including one of the nation’s first dedicated snakebite follow-up clinics, which treats patients in the hospital, provides follow-up, and studies new approaches and protocols in snakebite. They and their team are pioneering new methods that have resulted in greater peace of mind for patients and doctors alike.
“This is the nation’s very first comprehensive snakebite program,” said Shapshak, who also runs the UAB Comprehensive Wound Care Clinic, where he specializes in treating persistent wounds and swelling. Shapshak’s typical patient in the Comprehensive Wound Care Clinic is about 80 years old and is dealing with complications from diabetes or cancer.
“Our snakebite patients are much younger, from 5 to 30 or so; but the same techniques apply,” Shapshak said. “And they can make the difference between lifelong complications and a full recovery.”
The snakebite clinic provided follow-up treatment after snake envenomation to 17 patients in 2021. That includes a teenage cheerleader with lingering complications and a truck driver with severe envenomation and necrosis that threatened both his job and his ability to play guitar. The UAB Comprehensive Snakebite Program uses lower doses of antivenom and has shorter patient stays than many other hospitals, typically discharging patients in less than 24 hours. Follow-up visits to the snakebite clinic are now offered to any patient whose care triggers a call to APIC, regardless of insurance status.
Deep thinking on snakebites
The UAB Comprehensive Snakebite Program is staffed by toxicologists, wound-care experts, pharmacists and physical therapists. It cares for adults and children as young as 5.
“We will keep seeing people as long as they have persistent wounds and swelling,” Rushton said. “What we’re doing is cutting-edge. No one else is thinking this deeply about snakebites and follow-up.”
“Leaving the hospital after a snake envenomation experience can create a sense of ‘now what?’” Atti said. “Many patients find their questions unanswered, including ‘Do I elevate my limb? Do I do physical therapy? How long will the swelling last?’ and ‘When can I get back to work?’ I believe that having a place to follow up with snake envenomation experts provides comfort to patients that they are not on their own when they leave the hospital.”
The clinic is also reassuring for medical providers, adds Dr. Matthew Kelly, co-medical director for Wound Care and Hyperbaric Medicine at UAB.
“Snakebites are relatively rare, and any one provider may not see too many patients with complications from snakebites,” Kelly said. “With the snakebite clinic, we are able to see patients from throughout the state, and as with many things, experience is key in understanding the nuances of clinical care.”
Bites, blood and avoiding the knife
Snakebites in the United States are rarely fatal. Each year, between 7,000 and 8,000 Americans report being bitten by a snake, and on average, five will die. During Rushton’s seven years in Alabama, there have been very few snakebite deaths, and each of those had relatively unusual circumstances, he says. Snakebite season in Alabama and the Southeast runs from roughly mid-March to mid-November, and most bites occur in the evening.
About 10% of envenomations in Alabama are from rattlesnakes. The rest are from other pit vipers, including copperheads, cottonmouths and water moccasins. Doctors are quick to distinguish envenomation from the more all-encompassing term snakebite, because up to 50% of bites are dry, with no venom injected.
The most common complications from envenomation are local wound damage, swelling of extremities and severely painful blood blisters. When a snake envenomates a person, often on the foot, the tissues fill up with blood.
“For someone with little experience of snakebite, that swollen leg can look like dead, necrotic tissue that needs to be removed to avoid wider damage,” Rushton said. “That’s a hallmark of our program: to keep people away from unnecessary or harmful procedures. These large blood blisters are cared for by a wound-care specialist who has specific training of the mechanisms of envenomation. What we don’t want is someone trying to cut away that tissue, at least early on during active envenomation.”
Comprehensive, multidisciplinary snakebite care
The program’s multidisciplinary approach is what truly sets it apart, Rushton says. While patients are in the hospital, physical therapists emphasize early range-of-motion exercises and getting patients out of bed. Rushton says UAB pharmacy expertise has been crucial with the timing of the antivenom. Patients then get follow-up in the snakebite clinic and the benefit of the program’s research efforts.
The Comprehensive Snakebite Program is an innovator in the use of thromboelastography, or TEG, a method of precisely studying blood coagulation, clot strength and clot stability. TEG can provide a more rapid answer than traditional tests, such as prothrombin time and partial thromboplastin time tests. Because the Department of Emergency Medicine is a national leader in research, access to TEG is widespread enough that every snakebite patient admitted to UAB can receive the benefit of this technology, Rushton notes.
Even though rattlesnakes make up less than 10% of envenomation in the Southeast, rattlesnake bites can cause life-threatening coagulopathy.
“We don’t want to miss those,” Rushton said. “The reason we get TEGs on every snakebite patient is to screen for rattlesnake bites that may have been erroneously reported as copperhead bites. If that is the case, we will be more aggressive about giving antivenom. TEG can also be used to more precisely measure the antivenom dose, for the benefit of the patient, Rushton said.
Although the evidence is still out on whether TEGs are better than traditional labs, Rushton says the team can predict rattlesnake bites on the thromboelastogram earlier than from traditional coagulation markers.
“Snakebites can be intimidating to treat given all of the various scenarios in which patients can present,” Atti said. “Many community hospitals in the state of Alabama don’t have enough antivenom for more than one loading dose nor the means to care for a critically ill patient from a snake envenomation. This can create a lot of uncertainty for a community physician in trying to decide whether a patient needs to be transferred to another hospital for further care. We’re able to guide physicians in such scenarios, allowing them to make sound decisions.”
This story originally appeared on the UAB News website.
(Courtesy of Alabama NewsCenter)
Back in March, UAB and community partners joined in creating a research battalion as part of the fight to end the COVID-19 pandemic.
The UAB School of Medicine and the Hugh Kaul Precision Medicine Institute asked its researchers to submit proposals to compete for emergency COVID-19 grant money—funding that was raised through UAB and generous business donors in Birmingham and Montgomery.
The result? Twenty-eight ongoing projects, funded by $1.4 million in support, are exploring how the virus works, what might be a potential treatment, how to provide better testing, and more. (more…)
In early 2020, soon after it became clear that the COVID-19 pandemic was a serious threat to humanity, Kevin Harrod, Ph.D., the University of Alabama at Birmingham’s resident expert on SARS viruses, got a message from Matt Might, Ph.D., director of the university’s Precision Medicine Institute.
“If we computationally predict drugs, can you test them?” Might wanted to know. “I said ‘Sure,’” Harrod said.
Testing drugs on SARS-CoV-2, the novel coronavirus that causes COVID-19, requires more than a few petri dishes. Harrod’s lab operates at biosafety level 3, with scientists’ wearing full-body personal protective equipment that includes their own air supplies. (more…)
People who fight off COVID-19 carry a powerful memento in their blood: antibodies that are primed to wipe out the disease. By lending these trained immune soldiers to other patients, survivors might be able to knock out three cases of COVID for the price of one.
Antibody-rich blood plasma from people who have overcome COVID-19 is now helping to jumpstart immune defenses in patients struggling with the disease at UAB Hospital. Recently, UAB physicians treated three patients as part of an expanded-access clinical trial in collaboration with the Mayo Clinic, says Sonya Heath, M.D., professor of medicine in the Division of Infectious Diseases at the University of Alabama at Birmingham.
“The idea behind convalescent plasma is to take a donation from someone who had COVID-19 and recovered, and the immune response they developed may be able to help the patients who are treated with that plasma,” Heath said; she is the principal investigator at UAB for the study, which received expedited approval from the Food and Drug Administration in early April. Heath is working with Todd McCarty, M.D., assistant professor in the Division of Infectious Diseases, on the effort.
Could see benefit within 72 hours
The entire planet, more or less, is fixated on the greatest pandemic in modern memory. Claire Elliott is already preparing for the next one.
Elliott, a junior from Franklin, Tennessee, is part of UAB’s Undergraduate Immunology Program, one of a handful of such programs at universities in the United States. In high school, where she was part of an International Baccalaureate program, “my biology teacher was extremely passionate about the immune system,” Elliott said. “I heard about the immunology program at UAB and absolutely loved it.”
Elliott, who plans to apply to an accelerated master’s program at UAB next year, hopes to pursue clinical research or a job in public health or epidemiology. She is part of the first cohort of students in the program, which launched in fall 2017 and is a collaboration between the School of Medicine and the College of Arts and Sciences. (more…)